Oxycodone and Sertraline: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Oxycodone
Sertraline
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Taking oxycodone and sertraline together needs some care. Sertraline can slow down one of the liver enzymes (called CYP2D6) that helps break down oxycodone. That means more oxycodone can build up in your body, which can lead to stronger effects like heavy drowsiness or slowed, shallow breathing.
There's also a second concern. Both medicines raise a brain chemical called serotonin, and together they can rarely cause serotonin syndrome (things like shaking, fast heartbeat, sweating, confusion, or agitation). The good news is your care team can manage this by adjusting your dose and watching you closely. Don't stop either medicine on your own, but do check in with your doctor or pharmacist.
Effect: Increased oxycodone exposure plus additive serotonergic risk. Direction: increased opioid effect.
- Mechanism: Sertraline inhibits CYP2D6-mediated oxycodone metabolism, raising oxycodone plasma levels; both agents are serotonergic (additive PD effect).
- Onset/evidence: Delayed onset; evidence probable. Serotonin syndrome cases reported.
- Management: If coadministration is required, monitor frequently for sedation, respiratory depression, and serotonin syndrome, especially at initiation and dose changes. Consider oxycodone dose reduction until stable levels achieved. Discontinue oxycodone if serotonin syndrome suspected. If sertraline is stopped, watch for opioid withdrawal and consider increasing oxycodone. Strongly consider prescribing naloxone.
What happens
Increased oxyCODONE exposure and an increased risk of serotonin syndrome
Interaction Deep Dive
When sertraline, an inhibitor of CYP2D6, is given together with oxyCODONE, the opioid's effects may be intensified or extended. Such intensification can be greater if sertraline is introduced once a stable oxyCODONE dose has already been established. Since sertraline and oxyCODONE each act on the serotonergic neurotransmitter system, using them together may additionally give rise to serotonin syndrome. When combined therapy with oxyCODONE and sertraline is clinically necessary, monitor patients regularly for indications of sedation, respiratory depression, and serotonin syndrome, particularly at the start of treatment and when doses are being changed. A reduction in the oxyCODONE dose should be considered until stable plasma levels are reached. Should serotonin syndrome be suspected, stop oxyCODONE. If sertraline is stopped, watch for indications of opioid withdrawal and consider raising the oxyCODONE dose until stable drug effects are attained. Strongly consider prescribing naloxone for emergency management of opioid overdose. Serotonin syndrome, a condition that can be life-threatening, has been documented when opioids are used alongside serotonergic agents12. Concurrent administration of oxyCODONE and sertraline has led to symptoms consistent with serotonin syndrome3.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated oxyCODONE metabolism; additive serotonergic effects
How to manage this interaction
You can usually take both when your care team plans for it. Here is what they typically do:
- Watch you closely for excessive drowsiness, slowed breathing, or serotonin syndrome signs (agitation, sweating, shaking, fast heartbeat), especially when either drug is started or the dose changes.
- Your oxycodone dose may be adjusted and individualized until your levels are stable.
- They may prescribe naloxone as a safety backup for opioid overdose.
- If sertraline is later stopped, they may watch for opioid withdrawal and adjust oxycodone.
What you should do: Keep taking both as prescribed, don't change doses on your own, and promptly report any of the warning signs above to your pharmacist or prescriber.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) An 86-year-old woman developed features of serotonin syndrome after receiving oxyCODONE and sertraline together. She was admitted to hospital after a fall that caused a sacral fracture. Before admission, her medications consisted of extended-release oxyCODONE 10 mg twice daily and sertraline 150 mg once daily. To manage her pain, the oxyCODONE dose was raised to 20 mg twice daily, and after a short hospital stay she was moved to a long-term care facility for rehabilitation. Within a few days, she appeared agitated and exhibited markedly increased muscle tone in her lower extremities, truncal ataxia, and coarse tremors, along with myoclonic jerks in both feet. Sertraline was then rapidly tapered off and the oxyCODONE dose was reduced, which resolved the myoclonus, rigidity, and tremors within 2 days. It was suggested that the increase in the opiate dose may have triggered the serotonin syndrome in this patient 3.
b) A 34-year-old male bone marrow transplant patient had visual hallucinations and tremors after using sertraline together with high-dose oxyCODONE. Three days before presentation, the patient had been discharged from the hospital following an extensive workup (including a bone marrow biopsy) and treatment for pneumonia. His discharge medications were sertraline 50 mg once daily, oxyCODONE 10 mg as needed (average daily dose 10 to 20 mg/day), and cycloSPORINE 75 mg (total daily dose). He was also taking methylPREDNISolone, omeprazole, folinic acid, acyclovir, fluconazole, and trimethoprim/sulfamethoxazole. Within 48 hours after discharge, the patient took a total of 200 mg oxyCODONE over 48 hours for severe pain at the biopsy site, and during this period he had severe tremors and visual hallucinations. Because the patient had had similar tremors when cycloSPORINE therapy was started 1 year earlier and his current cycloSPORINE level was 467 ng/mL (388.31 nanomol/L), cycloSPORINE was thought to be the responsible agent, with a contribution from the narcotic use. Both cycloSPORINE and oxyCODONE were stopped and HYDROmorphone (maximum 6 mg/day) was started for pain control. However, 72 hours later, severe tremor and visual hallucinations, though to a lesser extent, persisted and the cycloSPORINE level had fallen to 128 ng/mL (106.4 nanomol/L). It was proposed that the increased oxyCODONE doses combined with sertraline use may have caused an increase in central serotonin. Sertraline was subsequently discontinued and oral cyproheptadine 8 mg was given, which resolved the hallucinations and reduced the tremor after 12 hours 4.
c) Instances of serotonin syndrome, a condition that can be life-threatening, have been reported when opioids are used together with serotonergic drugs 12.
Common questions
Can I take Oxycodone and Sertraline together?
Sertraline can raise oxycodone levels and add serotonin risk, so watch for heavy sedation, slowed breathing, or serotonin syndrome symptoms. Keep taking both as prescribed and let your care team adjust the dose and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Oxycodone and Sertraline interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Oxycodone and Sertraline interaction managed?
You can usually take both when your care team plans for it. Here is what they typically do: Watch you closely for excessive drowsiness, slowed breathing, or serotonin syndrome signs (agitation, sweating, shaking, fast heartbeat), especially when either drug is started or the dose changes. Your oxycodone dose may be adjusted and individualized until your levels are stable. They may prescribe naloxo… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
- How Long Should You Wait Between Metaxalone and Oxycodone?
- Can You Take Benadryl (Diphenhydramine) With Oxycodone?
- Does Oxycodone Expire?
- Switching Between Generic Sertraline Brands: What to Know
- Is Ashwagandha Safe With Bupropion, Sertraline And Azelastine?
- Converting Doses Of Lexapro (Escitalopram) To Zoloft (Sertraline)
Questions for your pharmacist
- Does my dose of Oxycodone or Sertraline need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (4)
- Product Information: OXYCONTIN(R) oral extended-release tablets, oxycodone HCl oral extended-release tablets. Purdue Pharma LP (per FDA), Stamford, CT, 2023. DailyMed
- Product Information: PERCODAN(R) oral tablets, oxycodone aspirin oral tablets. Endo Pharmaceuticals Inc. (per FDA), Malvern, PA, 2023.
- Gnanadesigan N, Espinoza RT, Smith R, et al: Interaction of serotonergic antidepressants and opioid analgesics: Is serotonin syndrome going undetected?. J Am Med Dir Assoc 2005; 6(4):265-269. DOI
- Rosebraugh CJ, Flockhart DA, Yasuda SU, et al: Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient. J Clin Pharmacol 2001; 41(2):224-227. PubMed
Keep reading about Oxycodone
Keep reading about Sertraline
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